Glucocorticosteroi
ds
Introduction to GS function
Endogenous and exogenous glucoticosteroids
Normal: 10-20mg/day
Treatment – not curative
MOA:
- Binds cytoplasmic glucocorticoid receptor.
- Affect gene expression.
- Via glucocorticoid response elements (GRE’s)
- Either induce or inhibit gene expression
Examples of affected genes
Transcription stimulation Transcription inhibition
Lipocortin (annexin-1) Cytokines: IL-1, IL-2, TNF-a, y-
, interferon, IL-6
Gluconeogenic pathway enzymes Phospholipase A2
Interleukin-2 receptor
Cyclooxygenase-2
Hypothalamic-pituitary-adrenal axis
CS induced Acute Adrenal crisis.
Cause: adrenal insufficiency (CS use>14 days)
Dose tapering-when use exceed 14 days.
Suppression of HPA axis by exogenous GS
- Triggers: stress, surgery, trauma, infection
- Symptoms:
Mild: myalgias, malaise, anorexia, weakness
Severe: vomiting fever, hypotension, shock
Management: parenteral hydrocortisone
Preserve HPA axis -alternate day dosing or morning dose.
Physiological response and adverse effects
Inflammatory response Susceptibility to
infections
Cancer
ds
Introduction to GS function
Endogenous and exogenous glucoticosteroids
Normal: 10-20mg/day
Treatment – not curative
MOA:
- Binds cytoplasmic glucocorticoid receptor.
- Affect gene expression.
- Via glucocorticoid response elements (GRE’s)
- Either induce or inhibit gene expression
Examples of affected genes
Transcription stimulation Transcription inhibition
Lipocortin (annexin-1) Cytokines: IL-1, IL-2, TNF-a, y-
, interferon, IL-6
Gluconeogenic pathway enzymes Phospholipase A2
Interleukin-2 receptor
Cyclooxygenase-2
Hypothalamic-pituitary-adrenal axis
CS induced Acute Adrenal crisis.
Cause: adrenal insufficiency (CS use>14 days)
Dose tapering-when use exceed 14 days.
Suppression of HPA axis by exogenous GS
- Triggers: stress, surgery, trauma, infection
- Symptoms:
Mild: myalgias, malaise, anorexia, weakness
Severe: vomiting fever, hypotension, shock
Management: parenteral hydrocortisone
Preserve HPA axis -alternate day dosing or morning dose.
Physiological response and adverse effects
Inflammatory response Susceptibility to
infections
Cancer
